Learn how to interpret and use intracranial EEG findings.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.

Targeted density electrode placement achieves high concordance with traditional high-density EEG for electrical source imaging in epilepsy.

OBJECTIVE: High-density (HD) electroencephalography (EEG) is increasingly used in presurgical epilepsy evaluation, but it is demanding in time and resources. To overcome these issues, we compared EEG source imaging (ESI) solutions with a targeted density and HD-EEG montage. METHODS: HD-EEGs from patients undergoing presurgical evaluation were analyzed. A low-density recording was created by selecting the 25 electrodes of a standard montage from the 83 electrodes of the HD-EEG and adding 8-11 electrodes around the electrode with the highest amplitude interictal epileptiform discharges. The ESI solution from this "targeted" montage was compared to that from the HD-EEG using the distance between peak vertices, sublobar concordance and a qualitative similarity measure. RESULTS: Fifty-eight foci of forty-three patients were included. The median distance between the peak vertices of the two montages was 13.2 mm, irrespective of focus' location. Tangential generators (n = 5/58) showed a higher distance than radial generators (p = 0.04). We found sublobar concordance in 54/58 of the foci (93%). Map similarity, assessed by an epileptologist, had a median score of 4/5. CONCLUSIONS: ESI solutions obtained from a targeted density montage show high concordance with those calculated from HD-EEG. SIGNIFICANCE: Requiring significantly fewer electrodes, targeted density EEG allows obtaining similar ESI solutions as traditional HD-EEG montage.

Neurophysiology, Neuropsychology, and Epilepsy, in 2022: Hills We Have Climbed and Hills Ahead. Neurophysiology in epilepsy.

Since the discovery of the human electroencephalogram (EEG), neurophysiology techniques have become indispensable tools in our armamentarium to localize epileptic seizures. New signal analysis techniques and the prospects of artificial intelligence and big data will offer unprecedented opportunities to further advance the field in the near future, ultimately resulting in improved quality of life for many patients with drug-resistant epilepsy. This article summarizes selected presentations from Day 1 of the two-day symposium "Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead". Day 1 was dedicated to highlighting and honoring the work of Dr. Jean Gotman, a pioneer in EEG, intracranial EEG, simultaneous EEG/ functional magnetic resonance imaging, and signal analysis of epilepsy. The program focused on two main research directions of Dr. Gotman, and was dedicated to "High-frequency oscillations, a new biomarker of epilepsy" and "Probing the epileptic focus from inside and outside". All talks were presented by colleagues and former trainees of Dr. Gotman. The extended summaries provide an overview of historical and current work in the neurophysiology of epilepsy with emphasis on novel EEG biomarkers of epilepsy and source imaging and concluded with an outlook on the future of epilepsy research, and what is needed to bring the field to the next level.

Interictal sleep recordings during presurgical evaluation: Bidirectional perspectives on sleep related network functioning.

Sleep recordings are an integral part of presurgical evaluation in drug-resistant focal epilepsy. Physiological network functioning is substantially different between wakefulness and sleep and thus may add further complexity to the task of determining the epileptogenic zone (EZ). A thorough understanding of changes in epileptic networks in relation to sleep is therefore essential in order to fully appreciate the added value of sleep recordings. Furthermore, shared expertise in epilepsy and sleep is beneficial for both domains, as intracerebral EEG during presurgical evaluation offers a unique window into physiological networks and their interaction during sleep. This review intends to delineate the way in which sleep modifies interictal epileptic discharges (IEDs), and to summarize which sleep state is the most appropriate for aiding in discerning the EZ. Two approaches will be reviewed. First, classical scalp electroencephalography (EEG) recordings help to localize the EZ, especially during rapid-eye-movement (REM) sleep. REM sleep tends to narrow the field size of IEDs, and thus helps to target the core of the EZ. Second, automated analysis of intracerebral recordings can make use of both IEDs and sleep-related oscillations in combination. Notably, high frequency oscillations and directed connectivity measures can be assessed in a single sleep cycle and are valuable tools to probe epileptogenicity. In this approach, which exploits increased network interactions during sleep, non-REM-sleep is the most suitable sleep stage to extract multiple features of local and distributed neuronal activity in order to predict the EZ. The added value of intracerebral recordings is perfectly bidirectional. From a sleep perspective, invasive EEG recordings are a unique opportunity to unravel local sleep-related network function of superficial and deeply situated brain structures. Intracerebral EEG has thus allowed the dissection of sleep features and oscillations and their anatomical sources. A multicenter effort led by the Montreal Neurological Institute resulted in a detailed open-access atlas on normative EEG activity during sleep (https://mni-open-ieegatlas.research.mcgill.ca/). It contributed to our understanding that the human brain does not sleep uniformly but that specifically deep structures have distinct signatures that are discernable from the rest of the brain. Also, this research direction allowed us to gain insights into our understanding of the important neurocognitive functions of sleep. Finally, this review provides a clinical outlook on the benefit of genuine sleep recordings, i.e. recordings with additional sleep sensors, concomitant to presurgical evaluation, in order to fully discern common sleep disorders as a frequent comorbidity of epilepsy. In conclusion, shared expertise in sleep and epilepsy is of mutual added value for improving the management of patients with epilepsy.

Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Functional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients. METHODS: Eighty-two patients with restless legs syndrome (untreated, n = 30; on dopaminergic medication, n = 42; on alpha-2-delta ligands as mono- or polytherapy combined with dopaminergic medication, n = 10), and 82 individually age- and gender-matched healthy controls were studied with resting-state functional magnetic resonance imaging. Connectivity of 12 resting-state networks was investigated with independent component analysis, and network topology was studied with graph methods among 410 brain regions. RESULTS: Patients with restless legs syndrome showed significantly higher connectivity within salience (p = 0.029), executive (p = 0.001), and cerebellar (p = 0.041) networks, as well as significantly lower (p < 0.05) cerebello-frontal communication compared to controls. In addition, they had a significantly higher (p < 0.05) clustering coefficient and local efficiency in motor and frontal regions; lower clustering coefficient in the central sulcus; and lower local efficiency in the central opercular cortex, temporal, parieto-occipital, cuneus, and occipital regions compared to controls. Untreated patients had significantly lower (p < 0.05) cerebello-parietal communication compared to healthy controls. Connectivity between the thalamus and frontal regions was significantly increased (p < 0.05) in patients on dopaminergic medication compared to untreated patients and controls. CONCLUSIONS: Networks with higher intranetwork connectivity (i.e., salience, executive, cerebellar) and lower cerebello-frontal connectivity in the restless legs syndrome patients, as well as lower cerebello-parietal connectivity in untreated patients, correspond to regions associated with attention, response inhibitory control, and processing of sensory information. Intact cerebello-parietal communication and increased thalamic connectivity to the prefrontal regions in patients on dopaminergic medication suggests a treatment effect on thalamus.

World Association of Sleep Medicine (WASM) 2016 standards for recording and scoring leg movements in polysomnograms developed by a joint task force from the International and the European Restless Legs Syndrome Study Groups (IRLSSG and EURLSSG).

This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM (PLM) are now defined by runs of at least four consecutive CLM with an intermovement interval ≥10 and ≤ 90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining CLM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoringof LM has only been altered by the new standards to require accepting all LM > 0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.

Parkinson's Disease Genetic Loci in Rapid Eye Movement Sleep Behavior Disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a prodromal condition for Parkinson's disease (PD) and other synucleinopathies, which often occurs many years before the onset of PD. We analyzed 261 RBD patients and 379 controls for nine PD-associated SNPs and examined their effects, first upon on RBD risk and second, on eventual progression to synucleinopathies in a prospective follow-up in a subset of patients. The SCARB2 rs6812193 (OR = 0.67, 95 % CI = 0.51-0.88, p = 0.004) and the MAPT rs12185268 (OR-0.43, 95 % CI-0.26-0.72, p = 0.001) were associated with RBD in different models. Kaplan-Meier survival analysis in a subset of RBD patients (n = 56), demonstrated that homozygous carriers of the USP25 rs2823357 SNP had progressed to synucleinopathies faster than others (log-rank p = 0.003, Breslow p = 0.005, Tarone-Ware p = 0.004). As a proof-of-concept study, these results suggest that RBD may be associated with at least a subset of PD-associated genes, and demonstrate that combining genetic and prodromal clinical data may help identifying individuals that are either more or less susceptible to develop synucleinopathies. More studies are necessary to replicate these results, and identify more genetic factors affecting progression from RBD to synucleinopathies.

Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.

OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Prevalence of restless legs syndrome in a Georgian primary healthcare setting: a pilot study.

BACKGROUND: The prevalence of restless legs syndrome (RLS) is approximately 10% in Western Europe, but unknown in Georgia. This pilot study aimed to assess RLS prevalence in a focused Georgian population. METHODS: An RLS epidemiological questionnaire [Allen et al.: Sleep Med 2003;4:101-119] was filled out by patients in five primary healthcare centers in two Georgian cities between March and September 2006. Additionally, questions related to RLS symptom onset, family history, treatment, sleep disturbance and history of iron deficiency were included. RLS diagnosis was based on an expert interview and an epidemiological questionnaire for RLS. RESULTS: The total number of respondents was 115 (75% women/25% men); mean age was 47 years (range 18-85). Thirteen subjects (11.3%) reported RLS symptoms (9 women/4 men); mean age was 52 years (range 32-83). Eleven (85%) had a positive family history of RLS. All subjects had sleep disturbance and none had a history of known iron deficiency. CONCLUSION: The prevalence of RLS in a focused Georgian population is in line with other RLS epidemiologic studies performed in clinical settings. However, the prevalence rate of RLS in a studied group might not be representative for the general Georgian population. Further population-based epidemiological studies are required.

Environmental risk factors for REM sleep behavior disorder: a multicenter case-control study.

OBJECTIVE: Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors for REM sleep behavior disorder. METHODS: Cases were patients with idiopathic REM sleep behavior disorder who were free of dementia and parkinsonism, recruited from 13 International REM Sleep Behavior Disorder Study Group centers. Controls were matched according to age and sex. Potential environmental and lifestyle risk factors were assessed via standardized questionnaire. Unconditional logistic regression adjusting for age, sex, and center was conducted to investigate the environmental factors. RESULTS: A total of 694 participants (347 patients, 347 controls) were recruited. Among cases, mean age was 67.7 ± 9.6 years and 81.0% were male. Cases were more likely to smoke (ever smokers = 64.0% vs 55.5%, adjusted odds ratio [OR] = 1.43, p = 0.028). Caffeine and alcohol use were not different between cases and controls. Cases were more likely to report previous head injury (19.3% vs 12.7%, OR = 1.59, p = 0.037). Cases had fewer years of formal schooling (11.1 ± 4.4 years vs 12.7 ± 4.3, p < 0.001), and were more likely to report having worked as farmers (19.7% vs 12.5% OR = 1.67, p = 0.022) with borderline increase in welding (17.8% vs 12.1%, OR = 1.53, p = 0.063). Previous occupational pesticide exposure was more prevalent in cases than controls (11.8% vs 6.1%, OR = 2.16, p = 0.008). CONCLUSIONS: Smoking, head injury, pesticide exposure, and farming are potential risk factors for idiopathic REM sleep behavior disorder.

Replication of restless legs syndrome loci in three European populations.

BACKGROUND: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q. METHODS: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms. RESULTS: We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26 x 10(-5), odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11 x 10(-5), OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9. CONCLUSION: Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.

Restless legs syndrome: a community-based study of prevalence, severity, and risk factors.

OBJECTIVE: To assess the prevalence and severity of restless legs syndrome (RLS) in the general community and to investigate its potential relationship with iron metabolism and other potential risk factors. METHODS: This was a cross-sectional study of a sex- and age-stratified random sample of the general population (50 to 89 years; n = 701). The diagnosis of RLS was established by face-to-face interviews; severity was graded on the RLS severity scale. Each subject underwent a thorough clinical examination and extensive laboratory testing. RESULTS: The prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression. None had been previously diagnosed or was on dopaminergic therapy. Free serum iron, transferrin, and ferritin concentrations were similar in subjects with and without RLS. However, soluble transferrin receptor (sTR) concentrations were different in subjects with and without RLS (1.48 vs 1.34 mg/L; p < 0.001). Female sex and high sTR independently predicted the risk of RLS. CONCLUSION: This large survey confirms the high prevalence, female preponderance, and underrecognition of restless legs syndrome in the general community. Although two-thirds of patients had moderate to severe disease, none was on current dopaminergic therapy.

Transient restless legs syndrome after spinal anesthesia: a prospective study.

OBJECTIVE: To assess the incidence and time course of new-onset restless legs syndrome (RLS) after spinal anesthesia. METHODS: A total of 202 consecutive patients undergoing spinal anesthesia for various types of surgery were prospectively evaluated regarding the presence and severity of RLS symptoms 48 to 72 hours post surgery and after 1 week, 1 month, 3 months, and 6 months. A diagnosis of RLS was made according to the criteria of the International RLS Study Group (IRLSSG), and severity was assessed by the IRLSSG severity scale. RESULTS: Of 161 patients without any history of RLS, 8.7% developed first-onset RLS after spinal anesthesia. Symptoms were transient, with a mean duration of 33 +/- 30 days. Low mean corpuscular volume and mean corpuscular hemoglobin were associated with the occurrence of new-onset RLS after spinal anesthesia. CONCLUSIONS: Transient RLS can be induced by spinal anesthesia. The mechanisms by which spinal anesthesia can trigger RLS are unclear but may include deficits in spinal sensorimotor integration in susceptible individuals.

Modafinil for the treatment of daytime sleepiness in Parkinson's disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial.

OBJECTIVES: To assess the therapeutic efficacy of modafinil in the treatment of increased daytime sleepiness in patients with Parkinson's disease (PD). DESIGN: Double-blind, randomized, placebo-controlled crossover study with two 2-week treatment blocks, separated by a 2-week washout phase. SETTING: Tertiary Parkinson's disease care center and sleep laboratory at university hospital neurology department. PATIENTS: Fifteen patients with idiopathic PD and daytime sleepiness (Epworth sleepiness score (ESS) 10 or more). INTERVENTIONS: Administration of placebo or modafinil as a single morning dose in a randomized crossover order. The modafinil dose was 100 mg in the first, and 200 mg in the second treatment week. MEASUREMENTS AND RESULTS: At baseline and at the end of each treatment block, sleepiness was evaluated using subjective (perceived sleepiness with the ESS) and objective measures (maintenance of wakefulness test). Twelve patients completed the study (9 male, 3 female; mean age 65.0 +/- 7.6 years, mean disease duration 6.8 +/- 4.1 years). Epworth scores were significantly improved with modafinil (3.42 +/- 3.90) compared to placebo (0.83 +/- 1.99; p = 0.011). Latency to sleep in the maintenance of wakefulness test was not significantly altered by modafinil treatment: 10.9 (3-40)/15.1 (2.5-40) minutes before/after placebo and 12 (2.6-40)/17.8 (4.2-40) minutes before/after modafinil (p = 0.139) [data given as mean +/- standard deviation or median (range)]. CONCLUSIONS: The results of this study suggest that modafinil improves daytime sleepiness in PD patients, at least on a subjective or behavioral level. Modafinil treatment may be considered for EDS in PD patients, in whom otherwise treatable causes of Excessive Daytime Sleepiness (EDS) are absent.